P-glycoprotein expression during tumor progression in the rat liver.

P-glycoprotein expression during tumor progression in the rat liver.
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发表时间:
1992-10
期刊:
影响因子:
11.2
通讯作者:
Grace Bradley;Radhakant Sharma;Srinivasan Rajalakshmi;Victor Ling
Grace Bradley;Radhakant Sharma;Srinivasan Rajalakshmi;Victor Ling
中科院分区:
医学1区
文献类型:
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作者:
Grace Bradley;Radhakant Sharma;Srinivasan Rajalakshmi;Victor Ling

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P-糖蛋白(P-Glycoprotein,Pgp)在肿瘤细胞系中介导多药耐药。在许多组织学类型的临床癌症样品中已经检测到Pgp的过表达。Pgp表达增加的基础和生物学意义尚不清楚。在这项研究中,Pgp的表达在逐步发展到大鼠肝癌进行了检查,以探讨Pgp在癌变过程中的可能作用。免疫组化技术被用来检测Pgp在单细胞水平,在大量的肝结节,肝细胞癌,并在远处转移的癌。结果表明,Pgp表达在逐步癌变过程中发生了明显的变化,这些变化与病变的显微解剖密切相关。相反,γ-谷氨酰转肽酶和谷胱甘肽S-转移酶-7.7,其表达似乎与早期肝癌的步骤,Pgp的表达是高的大增生结节和肝细胞癌比早期显微镜下病变。一个特别引人注目的发现是肺转移瘤中Pgp的一致表达。这些结果表明,Pgp与更进展的恶性表型在肝癌的发生。
P-Glycoprotein (Pgp) has been shown to mediate multidrug resistance in tumor cell lines. Overexpression of Pgp has been detected in clinical cancer samples of many histological types. The basis and biological significance of such increases in Pgp expression are not well understood. In this study, the expression of Pgp during stepwise progression to rat liver cancer was examined to investigate the possible role of Pgp in carcinogenesis. An immunohistochemical technique was used to detect Pgp at the single-cell level, in a large number of liver nodules, hepatocellular carcinoma, and in distant metastases of the carcinomas. The results showed that distinct changes in Pgp expression occurred during stepwise liver carcinogenesis and that these changes were closely associated with the microscopic anatomy of the lesions. In contrast to gamma-glutamyl transpeptidase and glutathione S-transferase-7.7, whose expression appeared to correlate with the early steps of liver carcinogenesis, Pgp expression was higher in the large hyperplastic nodules and in hepatocellular carcinomas than in the early microscopic lesions. A particularly striking finding was the consistent expression of Pgp in the lung metastases. These findings suggested that Pgp was associated with a more progressed malignant phenotype in liver carcinogenesis.